Opium alkaloids morphine

Opium alkaloids (morphine, codeine), acetylmorphine, oxyco-deinone, brucine, phenylbutazone, ketazone, trimethazone... 

Apomorphine hydrochloride (44 Apokyn Bertek, 2004), is a semisynthetic derivative of opium alkaloid morphine (43) isolated from poppy (Papaver somniferum), and it has long been known for its erectile activity at the effective dose of 2-6 mg physicians discovered the effect over 100 years ago, but found the drug, at a much higher dose (ca. 200 mg), to be more suitable for poison victims as an emetic because it also causes serious nausea and vomiting. Apomorphine exerts its erectile effect at the central nervous system the drug has been found to be a non-selective dopamine agonist which activates both Di-like and D2-like... 

The most widely used agonists in medical practice are the opium alkaloids morphine and codeine. However, semisynthetic derivatives (hydromorphone, oxymorphone, hydrycodon, oxycodone), whose use is even preferred in certain cases, and strong, purely synthetic compounds (methadone, meperidin, fentanyl, sufentanyl, and others) have found wide use. 

The opium alkaloid morphine is representative for this group of opiates and also for other opioid analgesics. Morphine is a full agonist for both the jx and the k receptors. It is used to relieve severe acute pain, or chronic pain in terminally ill patients. Its oral bioavailability varies from 15% to 35% and its... 

The opium alkaloids morphine, codeine, and thebaine have a phenanthrene nucleus (Figure 11.10 and Figure 11.11). 

Overman et al. exercised the CBS reduction strategy during synthesis of the natural opium alkaloid (—)-morphine (50)21 (Scheme 4.3q). Enantioselective reduction of 2-allylcyclohex-2-en-l-one (51) with catecholborane in the presence of the (R)-oxazaborolidinc catalyst (l )-28a provided the corresponding (S)-cyclohexenol 52 in greater than 96% ee. Condensation of this intermediate with phenyl isocyanate, regioselective catalytic dihydroxylation of the terminal double bond, and protection of the resulting diol afforded 53 in 68% overall yield from 51. The ally lie silane 54 for the upcoming iminium ion-ally lsilane cycliza-tion step was obtained in 81% yield by a stereoselective Sn2 displacement of allylic carbamate. 

For the identification of a number of opium alkaloids (morphine, codeine, thebaine, noscapine, papaverine, cryptopine, narceine) and heroin, 3-0-acetylmorphine, 6-0-acetylmorphine and acetyl codeine, Viala et al. 7 made use of three gas chromatographic columns of different polarities (SE-30 3 %, OV-1 2 % and OV-1 2 % plus Igepal 0.2 %).They obtained reliable separation and identification in this way, which was based on the difference in the retention times in the three columns. 

F.W.A. Sertiimer isolates principal opium alkaloid - morphine... 

Morphine bitartrate caused contact dermatitis in a worker at a plant production of opium alkaloids. Morphine hydrochloride and morphine bitartrate showed patch-test positive reactions in another patient with contact dermatitis working in the production of concentrated poppy straw. 

The idea that the opium alkaloid morphine is a modified benzyliso-quinoline provided the key to the structure 6.152) for the alkaloid twisting of the benzylisoquinoline skeleton into that shown for reticuline (6.127) in (6.148) illustrates this relationship and suggests a possible biogenesis. This was later proved correct in the course of a study which is one of the classics of alkaloid biosynthesis. In the first experiments ever to be carried out with complex plant-alkaloid precursors, [1- C]- and [S- Cj-norlaudanosoline [as (6.123) were fed to opium poppies [99, 100]. They were found to label morphine (6.152), codeine (6.153) and thebaine (6.151) specifically, thus establishing that these alkaloids are indeed benzylisoquinoline derivatives. The key intermediate [101] proved to be reticuline (6.148). Both (R) and (5)-isomers were utilized, the latter by way of (6.155) [101, 102] which allowed its conversion into (i )-reticuline (6.148), the correct intermediate, with the same configuration as the three opium alkaloids [as (6.151). ... 

An opium alkaloid Although it is an excellent analgesic its use is restricted because of the potential for addiction Heroin is the diacetate ester of morphine )... 

Opioids. Morphine [57-27-2] C yH NO, (8) the most prevalent and analgesicaHy potent of the naturally occurring opium alkaloids (qv), has been used as an anesthetic premedication for over one hundred years (93). It has also been used as an iv analgesic for the last four decades, and, since 1969, in high doses as an anesthetic agent (117). 

Noscapine [128-62-1] (45) is the second most abundant alkaloid found in opium. Unlike most opium alkaloids, however, it has an isoquinoline rather than a phenanthrene ting system. Noscapine was first isolated in 1817 but its antitussive activity was not demonstrated pharmacologically until 1952 (63). Clinical studies have confirmed its effectiveness. It is not a narcotic and has a wide margin of safety when given orally. Death could be produced in rats only with doses > 800 mg/kg (64). Noscapine is isolated from the water-insoluble residue remaining after processing opium for the manufacture of morphine. 

The first scheme for the separation of the six chief alkaloids of opium, VIZ., morphine, codeine, thebaine, papaverine, narcotine and narceine, is probably that of Plugge. Much later Kljatschkina investigated for each of these six bases the properties by means of which isolation and estimation could probably be effected and, on the basis of the results, devised a plan for such analyses. More recently Anneler has published a detailed account of a scheme with the same objective. l Attention had already been given to complex, systematic analyses of this kind, in connection with examination of the mixtures of opium alkaloids, which have long been in use in medicine in these at first only morphine and other alkaloids were determined, but in the more recent schemes provision is made for the estimation of each alkaloid. ... 

The processes used in the manufacture of morphine are believed to be still based on that described by the Scottish chemist Gregory,in 1833, with improvements devised by Anderson. A description has been published by Schwyzer, who also deals with the manufactme of codeine, narcotine, cotarnine, and the commercially important morphine derivatives, diamorphine (diacetylmorphine), and ethylmorphine (morphine ethyl ether). More recently Barbier has given an account of processes, based on long experience in the preparation of alkaloids from opium. Kanewskaja has described a process for morphine, narcotine, codeine, thebaine and papaverine, and the same bases are dealt with by Chemnitius, with the addition of narceine, by Busse and Busse, and by Dott. It is of interest to note that a number of processes for the extraction and separation of opium alkaloids have been protected by patent in Soviet Russia. ... 

A characteristic feature of the action of the opium alkaloids is their simultaneous depressing and exciting action on the central nervous system. In this respect there is no clear line of demarcation between the morphine group—morphine, codeine and thebaine—and the papaverine-narcotine group, and as the series is ascended in the order, morphine, papaverine, codeine, narcotine, thebaine, narcotic action diminishes and power of rellex stimulation increases until in thebaine a strychnine-like effect is exhibited. 

RISK FDR INJURY. Narcotics may produce orthostatic hypotension, which in turn results in dizziness. The nurse should assist the patient with ambulatory activities and with rising slowly from a sitting or lying position. Miosis (pinpoint pupils) may occur with the administration of some narcotics and is most pronounced with morphine, hydro mo rpho ne, and hydrochlorides of opium alkaloids. Miosis decreases the ability to see in dim light. The nurse keeps the room well lit during daytime hours and advises the patient to seek assistance when getting out of bed at night. 

Rice, K.C. (1980) Synthetic Opium Alkaloids and Derivatives. A Short Total Synthesis of (ib)-Dihydrothebainone, ( )-Dihydrocodeinone, and ( )-Nordihydrocodemone as an Approach to a Practical Synthesis of Morphine, Codeine, and Congeners. Journal of Organic Chemistry, 45, 3135-3137. 

Hong, C.Y, Kado, N., Overman, L.E. (1993) Asymmetric Synthesis of Either Enantiomer of Opium Alkaloids and Morphinans. Total Synthesis of (—)- and (-f)-Dihydrocodeinone and (—)- and (-F)-Morphine. Journal of the American Chemical Society, 115, 11028-11029. 

More than 30 alkaloids have been identified in opium (Robbers et al. 1996). The most relevant are morphine (4-21%), codeine (0.8-2.5%), noscapine (4-8%), papaverine (0.5-2.5%), and thebaine (0.5-2%) (figure 8.4). Other opium alkaloids include narceine, protopine, laudanine, codamine, cytopine, lanthopine, and meconidine. Numerous other opioids have been synthesized from opium alkaloids. Among them is heroin, or diacetylmorphine. 

Opioids are administered in several ways. Opium was most commonly taken recreationally by smoking, but intravenous administration has become most common since the isolation of opium alkaloids and invention of the hypodermic needle. The development of heroin from morphine at the turn of the twentieth century led to more intense euphoric effects and greater risk for addiction. Heroin may also be snorted, or it can be smoked when added to a medium such as tobacco. Medically, opioids are commonly given through oral, subcutaneous, intravenous, transdermal, or rectal routes. 

In the first place, the structure of the target molecule is submitted to a rational analysis in order to perceive the most significant structural features, and it may be useful to use different types of molecular models at this point. It should be remembered that a molecular structure has "thousand faces" and finding the most convenient perspective may greatly simplifly the synthetic problem. The synthesis of opium alkaloids, for instance, is much simplified if one realises that they are, in fact, derivatives of benzyltetrahydroisoquinoline (18) (see Scheme 3.8). This was indeed the inspired intuition of Sir Robert Robinson which led to the structural elucidation of morphine (19) and to a first sketch of the biogenetic pathway [22], and later on to the biomimetic synthesis of thebaine 20 [23] [24]. 

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